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This
review explores similarities between lymphocytes and cancer cells, and
proposes a new model for the genesis of human cancer.
We suggest that the development of cancer requires infection(s) during
which antigenic determinants from pathogens mimicking self-antigens
are co-presented to the immune system, leading to breaking T cell
tolerance.
Some level of autoimmunity is normal and necessary for effective
pathogen eradication.
However, autoreactive T cells must be eliminated by apoptosis when the
immune response is terminated.
Apoptosis can be deficient in the event of a weakened immune system,
the causes of which are multifactorial.
Some autoreactive T cells suffer genomic damage in this process, but
manage to survive.
The resulting cancer stem cell still retains some functions of an
inflammatory T cell, so it seeks out sites of inflammation inside the
body.
Due to its defective constitutive production of inflammatory cytokines
and other growth factors, a stroma is built at the site of
inflammation similar to the temporary stroma built during wound
healing.
The cancer cells grow inside this stroma, forming a tumor that
provides their vascular supply and protects them from cellular immune
response.
As
cancer stem cells have plasticity comparable to normal stem cells,
interactions with surrounding normal tissues cause them to give rise
to all the various types of cancers, resembling differentiated tissue
types.
Metastases form at an advanced stage of the disease, with the
proliferation of sites of inflammation inside the body following a
similar mechanism.
Immunosuppressive cancer therapies inadvertently re-invigorate
pathogenic microorganisms and parasitic infections common to cancer,
leading to a vicious circle of infection, autoimmunity and malignancy
that ultimately dooms cancer patients.
Based on this new understanding, we recommend a systemic approach to
the development of cancer therapies that supports rather than
antagonizes the immune system.
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